Non-invasive Brain Stimulation for Dementia

(ACDCStim Trial)

Overseen by Brad Manor, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Hebrew SeniorLife

Must not be taking: Neuroactive drugs

Disqualifiers: Major psychiatric disorders, Seizures, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a home-based brain stimulation treatment using gentle electrical currents to improve memory, movement, and thinking skills in older adults with early-stage memory problems. Caregivers are trained to administer the treatment at home. This method has been widely studied for its potential to enhance cognitive function in older adults, including those with neurodegenerative diseases like Alzheimer's.

Will I have to stop taking my current medications?

The trial excludes participants using neuroactive drugs, so you may need to stop taking such medications to participate. However, the protocol does not specify a washout period.

What data supports the effectiveness of the treatment Non-invasive Brain Stimulation for Dementia?

Research suggests that transcranial direct current stimulation (tDCS), a type of non-invasive brain stimulation, may help improve cognitive functions in elderly people with age-related cognitive decline, including those with dementia. However, the evidence is not yet strong enough to draw firm conclusions, and more studies are needed to confirm its effectiveness. ^{1 2 3 4 5}

Is non-invasive brain stimulation safe for humans?

Non-invasive brain stimulation techniques like tDCS and tACS are generally considered safe, with mild side effects such as headaches and skin sensations. Serious side effects are rare, and the safety profile is similar across different groups, including the elderly and those with neurological conditions. ^{6 7 8 9 10}

How is non-invasive brain stimulation different from other treatments for dementia?

Non-invasive brain stimulation, like transcranial direct current stimulation (tDCS), is unique because it uses a low-dose electrical current to modulate brain function without surgery or medication. This method is low-cost, portable, and easy to use, making it more accessible compared to other treatments that might be more expensive or less available. ^{2 3 6 11 12}

Research Team

Alvaro Pascual-Leone, MD; PhD

Principal Investigator

Hebrew SeniorLife

Brad Manor, PhD

Principal Investigator

Hebrew SeniorLife

Eligibility Criteria

This trial is for older adults with mild cognitive impairment or mild dementia who can read, write, and communicate in English. They must have a caregiver willing to learn and administer brain stimulation treatments. Participants should not have severe psychiatric disorders, major vision impairments, skin conditions on the scalp, or score below 18 on the MoCA test.

Inclusion Criteria

I am willing and able to consent to participate in the study.

Caregiver/Administrators must have self-reported computer proficiency and willingness to learn how to use tES as defined by 'yes' answers to specific questions

My caregiver is available on weekdays to help with my treatment.

Exclusion Criteria

Participants must not have contraindications to tES, as recorded on a standardized screening questionnaire

I do not have any disabilities that stop me from performing tasks.

Caregiver/Administrators must not have mild cognitive impairment defined by a MoCA score ≤26 during the in-person screen

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-intervention assessments

Participants undergo a set of assessments before the intervention begins

1 week

Treatment

Participants receive daily home-based brain stimulation intervention for 4 weeks

4 weeks

20 sessions (home-based)

Post-intervention assessments

Participants undergo assessments immediately following the brain stimulation intervention

1 week

Follow-up

Participants are monitored for safety and effectiveness at 3 and 6 months post-intervention

6 months

Treatment Details

Interventions

• Non-invasive Brain Stimulation (Non-invasive Brain Stimulation)

Trial Overview The study tests if remote brain stimulation by caregivers can improve memory, mobility, and executive function in dementia patients. It involves active/sham transcranial direct current (tDCS) and alternating current (tACS) stimulations to see which combination is effective.

Participant Groups

Group I: tACS(AG) + tDCS(PFC) combo active Experimental Treatment 1 Intervention

Participants (Ps) will undergo 20min of daily home-based tACS active + tDCS active intervention over the left angular gyrus and prefrontal cortex for 4 weeks by their trained caregiver/administrators (As).

Group II: tACS(AG) active + tDCS(PFC) sham Active Control 1 Intervention

Participants (Ps) will undergo 20min of daily home-based tACS active + tDCS sham intervention over the left angular gyrus and prefrontal cortex for 4 weeks by their trained caregiver/administrators (As).

Group III: tACS(AG) sham + tDCS(PFC) active Active Control 1 Intervention

Participants (Ps) will undergo 20min of daily home-based tACS sham + tDCS active intervention over the left angular gyrus and prefrontal cortex for 4 weeks by their trained caregiver/administrators (As).

Group IV: tACS(AG) sham + tDCS(PFC) sham Placebo Group 1 Intervention

Participants (Ps) will undergo 20min of daily home-based tACS sham + tDCS sham intervention over the left angular gyrus and prefrontal cortex for 4 weeks by their trained caregiver/administrators (As).

Who Is Running the Clinical Trial?

Hebrew SeniorLife

Lead Sponsor

Trials

52

Recruited

273,000+

BrightFocus Foundation

Collaborator

Trials

5

Recruited

430+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Dr. Richard J. Hodes

National Institute on Aging (NIA)

Chief Executive Officer since 1993

MD from Harvard Medical School

Dr. Marie Bernard

National Institute on Aging (NIA)

Chief Medical Officer

MD from Harvard Medical School

Findings from Research

Transcranial direct current stimulation (tDCS) has shown promise in enhancing cognitive functions, particularly declarative and working memory, in elderly individuals experiencing cognitive decline, based on a review of 16 studies.

Standardized tDCS protocols, specifically applying 2 mA for 30 minutes over the left dorso-lateral prefrontal cortex, appear to be effective in slowing cognitive deterioration, although individual differences necessitate personalized adjustments for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Methods, Old Brains-A Systematic Review on the Effects of tDCS on the Cognition of Elderly People. Siegert, A., Diedrich, L., Antal, A.[2021]

In a pilot study involving 30 older adults with depression and/or anxiety, transcranial direct current stimulation (tDCS) significantly improved executive functioning, particularly inhibitory processing and cognitive flexibility, as evidenced by better performance on the Stroop test and Trail Making Test-Part B.

The study suggests that tDCS may be a promising non-invasive treatment to enhance cognitive processing in geriatric patients, although it did not show significant effects on attention or working memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

tDCS over the left prefrontal Cortex improves mental flexibility and inhibition in geriatric inpatients with symptoms of depression or anxiety: A pilot randomized controlled trial. Figeys, M., Villarey, S., Leung, AWS., et al.[2022]

A meta-analysis of 4 studies found that transcranial direct current stimulation (tDCS) alone did not significantly improve the naming ability of patients with dementia.

However, when tDCS was combined with language or cognitive training, it resulted in a large effect size (SMD=0.72), indicating a significant improvement in naming ability for dementia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Effects of tDCS and Language/Cognitive Intervention on the Naming of Dementia Patients: A Systematic Review and Meta-Analysis. Byeon, H.[2022]

Multisession anodal tDCS showed no significant improvement in global cognition or specific cognitive domains in patients with Alzheimer's disease and mild cognitive impairment, with mean differences of -0.13 points and -0.53 points respectively, indicating limited efficacy.

The review included eight studies, highlighting a need for more extensive research with larger sample sizes and standardized outcome measures to better assess the effectiveness of tDCS in cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Meta-Analysis of the Effect of Multisession Transcranial Direct Current Stimulation on Cognition in Dementia and Mild Cognitive Impairment. Inagawa, T., Narita, Z., Sugawara, N., et al.[2022]

In a study involving 34 patients with mild cognitive impairment (MCI), those receiving 20 days of anodal transcranial direct current stimulation (tDCS) showed significant improvements in cognitive functions, including episodic verbal memory and overall cognitive function, compared to a sham group.

The results suggest that anodal tDCS may enhance cognitive symptoms in MCI patients, indicating its potential as a therapeutic tool, although further research is needed to clarify the underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects on cognition of 20-day anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex in patients affected by mild cognitive impairment: a case-control study. Fileccia, E., Di Stasi, V., Poda, R., et al.[2020]

Transcranial direct current stimulation (tDCS) shows potential as a non-invasive treatment for improving memory in elderly individuals with mild cognitive impairment or Alzheimer's disease, but only five out of 13 studies reviewed demonstrated positive effects.

The study highlighted significant variability in tDCS protocols and noted methodological weaknesses, indicating a need for more rigorous research to better understand the effectiveness and long-term benefits of tDCS on memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Transcranial Direct Current Stimulation on Memory of Elderly People with Mild Cognitive Impairment or Alzheimer's Disease: A Systematic Review. da Silva, ER., Rodrigues Menezes, IR., Brys, I.[2022]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

Transcranial direct current stimulation (tDCS) was found to be safe and well-tolerated in a study involving 20 patients with mild or major neurocognitive disorders, with an attrition rate of 0% and no serious adverse events reported.

However, the study did not find any statistically significant improvements in cognitive functioning when comparing the active tDCS group to the sham group, indicating that tDCS may not enhance cognitive performance in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of Transcranial Direct Current Stimulation for Cognitive Rehabilitation in Patients With Mild or Major Neurocognitive Disorders: A Randomized Sham-Controlled Pilot Study. Inagawa, T., Yokoi, Y., Narita, Z., et al.[2022]

A systematic review of 64 studies involving 2262 participants found that transcranial direct current stimulation (tDCS) has a low dropout rate (6% for active and 7.2% for sham), indicating good acceptability among participants.

Despite the low dropout rates, many studies inadequately reported adverse events (AEs), highlighting a need for improved guidelines to standardize AE reporting in tDCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. Aparício, LVM., Guarienti, F., Razza, LB., et al.[2018]

Transcranial Direct Current Stimulation (tDCS) is generally considered safe, but there are concerns that it could lead to significant negative effects in healthy individuals.

The scientific community needs to be alerted about the potential risks of tDCS, emphasizing the importance of protecting healthy volunteers from possible harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial direct current stimulation in healthy participants. Boccard-Binet, S., Sen, A.[2021]

Noninvasive brain stimulation (NIBS) techniques, particularly repetitive transcranial magnetic stimulation (rTMS), significantly improved behavioral and psychological symptoms of dementia (BPSD) immediately after treatment, with a moderate effect size based on a meta-analysis of 10 studies involving 324 patients.

While rTMS showed lasting benefits at follow-up visits, transcranial direct current stimulation (tDCS) did not demonstrate significant improvements, indicating that rTMS may be a more effective option for managing BPSD in dementia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of noninvasive brain stimulation for behavioral and psychological symptoms of dementia: a systematic review and meta-analysis. Wang, X., Mao, Z., Yu, X.[2021]

Transcranial direct current stimulation (tDCS) is a low-cost and portable technique that can modulate brain function, making it a promising tool for treating psychiatric disorders.

While tDCS has been widely used in research to study brain processes, its specific effects on psychiatric patients are not well understood, highlighting the need for further investigation into its mechanisms of action and optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The application of tDCS in psychiatric disorders: a brain imaging view. Baeken, C., Brunelin, J., Duprat, R., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

New Methods, Old Brains-A Systematic Review on the Effects of tDCS on the Cognition of Elderly People. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

tDCS over the left prefrontal Cortex improves mental flexibility and inhibition in geriatric inpatients with symptoms of depression or anxiety: A pilot randomized controlled trial. [2022]

3. Iran pubmed.ncbi.nlm.nih.gov

Combined Effects of tDCS and Language/Cognitive Intervention on the Naming of Dementia Patients: A Systematic Review and Meta-Analysis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A Meta-Analysis of the Effect of Multisession Transcranial Direct Current Stimulation on Cognition in Dementia and Mild Cognitive Impairment. [2022]

5. Italy pubmed.ncbi.nlm.nih.gov

Effects on cognition of 20-day anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex in patients affected by mild cognitive impairment: a case-control study. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Effects of Transcranial Direct Current Stimulation on Memory of Elderly People with Mild Cognitive Impairment or Alzheimer's Disease: A Systematic Review. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of Transcranial Direct Current Stimulation for Cognitive Rehabilitation in Patients With Mild or Major Neurocognitive Disorders: A Randomized Sham-Controlled Pilot Study. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Safety of transcranial direct current stimulation in healthy participants. [2021]

11. Italy pubmed.ncbi.nlm.nih.gov

The role of noninvasive brain stimulation for behavioral and psychological symptoms of dementia: a systematic review and meta-analysis. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

The application of tDCS in psychiatric disorders: a brain imaging view. [2020]